title: Primary 4T1 tumor resection provides critical "window of opportunity" for immunotherapy.
abstract: It is believed that primary tumor resection modulates host-tumor immune interaction, but this has not been characterized in a stringent breast cancer tumor model. This report, using the 4T1 murine mammary tumor model, characterizes for the first time the dynamic longitudinal changes in immunosuppressive and effector components of the immune system after resection of an established orthotopic primary tumor with a defined natural history of developing lung metastases. More specifically, we analyzed changes of absolute numbers and frequencies of MDSC, regulatory T cells (Treg), as well as activated CD4 and CD8 positive T cells in spleens and, in some studies, lungs of 4T1 tumor-bearing mice and mice after primary tumor resection. Importantly, using mathematical analyses we established that primary resection of an orthotopic tumor had created a "window of opportunity" with decreased tumor-associated immune suppression that existed for approximately 10 days. Although tumor resection did slightly prolong survival, it did not affect the ultimate development of metastatic disease since animals with resected tumors or intact primary tumors eventually died by day 47 and 43, respectively. This window of opportunity likely occurs in humans providing a rationale and parameters for integration and testing of immunotherapeutic strategies in this critical "window of opportunity" to combat the development of metastatic disease.
authors.affiliation: Department of Molecular Immunology, Institute for Molecular Medicine, 16371 Gothard Street, Suite H, Huntington Beach, CA, 92647, USA, aghochikyan@immed.org.
authors.forename: Anahit
authors.initials: A
authors.lastname: Ghochikyan
authors.forename: Arpine
authors.initials: A
authors.lastname: Davtyan
authors.forename: Armine
authors.initials: A
authors.lastname: Hovakimyan
authors.forename: Hayk
authors.initials: H
authors.lastname: Davtyan
authors.forename: Anna
authors.initials: A
authors.lastname: Poghosyan
authors.forename: Alexander
authors.initials: A
authors.lastname: Bagaev
authors.forename: Ravshan I
authors.initials: RI
authors.lastname: Ataullakhanov
authors.forename: Edward L
authors.initials: EL
authors.lastname: Nelson
authors.forename: Michael G
authors.initials: MG
authors.lastname: Agadjanyan
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D007167:Immunotherapy; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000601:surgery* / Q000628:therapy*; D051379:Mice